: Significant or not really depends on the user but the intuos4 certainly has changed a bit since its previous version. increased sensibility (2048 levels instead of previously 1024) I'm not

Significant or not really depends on the user but the intuos4 certainly has changed a bit since its previous version.

increased sensibility (2048 levels instead of previously 1024) I'm not noticing this much. But might be just my blunt nature.
The design and button layout has changed a lot. Now it is useable for both left and right handed people. The intuos3 was also but acomplished this by replicating the same buttons + powerstrip on BOTH sides rendering one set of buttons not-really-useable (at least for me). Now all buttons and the touch strip(ring) are placed to one side but the design allows you to switch the tablet so the buttons end up either on the right or left. I no longer have the feeling of "waisting" good buttons.
Buttons. Intuos3 had the ability to map two functions on each button assigning on of them to switch between these functions. This is no longer possible in the intuos4.
BUT The Intuos4 introduces the use of a radial menu which can have several sub-menus all customizable with functions. Providing far more functions (alltough not so readilly available) than before.
An additional feature is also the touchring which is actually a evolution of the straight (up - down) touchstrip. This ring is imo better suited for its use since you can map it to zoom in + out. rotate canvas, sizeup-down, etc.. it seems more logical to assign these functions to something the turns like a dial than a lever-movement.
Another additional and quite distinctive element are the OLED displays besides the buttons that show you the functions assigned to them (although their unnervingly uncustomizability only show text, no custom icons). This is usefull when switching between programs which have different mappings. Most times you'll remember though.
I like the all-black design better than the grey Intuos3
Intuos4 comes with an "inkpot" like stand where you can rest your pen either horizontally or vertically and which doubles as a container for spare tips and pliers.
Tips. The intuos 4 pentips or nibbles or whatever their name wear noticeably faster on the intuos4 surface which in turn feels and sounds more paper-like (to me. Other people might disagree). The surface of my intuos4 on the other hand shows less wear than I think my intuos3 showed after the same amount of use (intuos3 got a quite shiny look on the surface after aprox 6months of use). I have the Intuos4 for nearly a year and barely see some scratches on the still-matte surface.
I have the wired Intuos4 but there is a intuos4 Medium which operates wirelessly (via bluetooth, i believe)
The pen also changes but for better or worse I can't really tell. Just different. lighter on the 4
The aspectratio of the intuos 4 is widescreen (16:9) whereas the intuos3 is available also in 4:3 depending on the chosen size. This might prove to be a big deal if you are doing illustration work and depend on using the whole canvas.

I think the intuos4 has a sleeker look and fits better on my desk with my Dell StudioXPS (black body silver-lined) laptop. But that really is just unimportant.
I tend to travel more with the Intuos4 than before. Maybe because it's more slim or because it has the same height and width as my laptop and fits snuggly into the pocket of the sleeve. I'm quite happy with this version of the intuos and the changes made but wouldn't think it necesary to upgrade. I believe I could be as happy if I still possessed the intous3 (it was not mine. provided by my employer)

Finally I'd like to add that these points are in no particular order of importance. I wrote them down just as I were remembering them.

Hope this helps. If you have questions about specific aspects please let me know!